NM_001005388.3:c.-91+5855A>T

Variant names:

• chr1-204926595-A-T
• rs1055679797
• NM_001005388.3:c.-91+5855A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001005388.3(NFASC):​c.-91+5855A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 29)
• Consequence: NFASC NM_001005388.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 0 publications found

Genes affected

NFASC (HGNC:29866): (neurofascin) This gene encodes an L1 family immunoglobulin cell adhesion molecule with multiple IGcam and fibronectin domains. The protein functions in neurite outgrowth, neurite fasciculation, and organization of the axon initial segment (AIS) and nodes of Ranvier on axons during early development. Both the AIS and nodes of Ranvier contain high densities of voltage-gated Na+ (Nav) channels which are clustered by interactions with cytoskeletal and scaffolding proteins including this protein, gliomedin, ankyrin 3 (ankyrin-G), and betaIV spectrin. This protein links the AIS extracellular matrix to the intracellular cytoskeleton. This gene undergoes extensive alternative splicing, and the full-length nature of some variants has not been determined.[provided by RefSeq, May 2009]

NFASC Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with central and peripheral motor dysfunction

  Inheritance: AR, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005388.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFASC	NM_001005388.3	MANE Select	c.-91+5855A>T		intron	N/A	NP_001005388.2	O94856-9
	NFASC	NM_001160331.2	MANE Plus Clinical	c.-90-17631A>T		intron	N/A	NP_001153803.1	O94856-11
	NFASC	NM_001378329.1		c.-91+5855A>T		intron	N/A	NP_001365258.1	O94856-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFASC	ENST00000339876.11	TSL:5 MANE Select	c.-91+5855A>T		intron	N/A	ENSP00000344786.6	O94856-9
	NFASC	ENST00000539706.6	TSL:5 MANE Plus Clinical	c.-90-17631A>T		intron	N/A	ENSP00000438614.2	O94856-11
	NFASC	ENST00000401399.5	TSL:1	c.-91+5855A>T		intron	N/A	ENSP00000385637.1	O94856-9

Frequencies

GnomAD3 genomes Cov.: 29

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.0
DANN	Benign	0.73
PhyloP100		-1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1055679797; hg19: chr1-204895723;